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What the next generation medication management in clinical trials should entail and insights on smart technologies and synergistic partnerships—backed by real-life implementation use cases.
Medications don’t work for patients who don’t take them – C. Everest Koop1
The above statement may sound as a no-brainer. Unfortunately, medication adherence continues to remain one of the biggest healthcare challenges not only for commercially available treatments but also for Investigational Medicinal Products (IMPs) in clinical trials. Research has shown that, across all therapeutic areas, adherence rates drop by 40% within a year of clinical trial commencement.
Incorrect medication intake can pose multiple risks such as sub-optimal therapeutic effects, higher chance of side effects, increased use of medical resources, or even incorrect assessments and conclusions for the Investigational Medicinal Products with an early termination of potential life-saving compounds.2,3
Physicians too have limited to no real-time insights into the activities at home, and hence incorrect intake is picked up only during the next interaction or a few even go unnoticed. This can have a significant impact on the safety and health of patients.
While patient medication adherence has its set of challenges, life sciences organizations worldwide too are grappling with a highly complex and convoluted medication process that involves multiple stakeholders, isolated systems, manual, and often paper-based processes resulting in a labor-intensive, costly, and error-prone process. To give an example, 20-25% of on-site monitoring activities are linked with IMP handlings including verifying documents related to kit receipt, dispensing, return, destruction, manual pill counts, patient medication diaries, and so on. Inadequate drug accountability is attributed as one of the top five major inspection findings4,5 behind inadequate patient medication adherence.
In addition, IMPs are traditionally prepared at the study level requiring overage calculations to ensure sufficient stock at a global level. This, coupled with the regular needs for relabeling, (i.e., linked with new IMP stability data) results in significant supply waste. Studies have shown that typically at least 20-40% of prepared IMPs are never used by a patient.6,7
And lastly, due to the COVID-19 pandemic, the already complex medication flows have been further disrupted. Alternative delivery methods to ship IMPs directly to the patient’s home or local pharmacies were put in place to ensure continued access to study drug. Virtual mechanisms to explain dosing regimen, digital enablement for medication intake and verification, involvement of home nurses, etc. are just a few examples of methodologies that were embraced in a record time to ensure continuity. Many of these technologies are not new but were unable to pass the prototype stage pre-COVID, as there were always the big “what if”, “can we do this”, “show me your business model/ROI” questions that halted broader roll out.
In this article, we will get a flavor of what the next generation medication management in clinical trials should entail and share some insights on smart technologies and synergistic partnerships, backed by real-life implementation use cases. We shall look at three key tenets to enable smart medication management:
Complicated treatment regimen, complex and difficult-to-understand medication instructions, limited to no personalized support, and lack of real-time insights into the happenings at home are just a few factors that can increase patient non-adherence.2,3 To give an example, currently multilingual medication booklet labels are used as standard in clinical trials. These medication booklet labels usually run up to 60 pages with each official language in any country requiring a separate label, the print font is extremely small, and information shared is incomplete (e.g., for dosing instructions, the patient needs to consult another document). It is therefore no surprise that patients have a hard time understanding and complying to medication instructions. Many booklet labels are hence returned unopened by patients.7
But the good news is that many smart technology investments and cross-industry partnerships have happened in this area enabling a more patient-tailored approach.
Personalized notifications specifying details of when and how to consume the medication, multimedia tools such as hands-on and easy-to-understand instructions and educational videos in patient’s native language, accessible anytime, anywhere, using their own smartphone can guide patients in a personalized way throughout their medication intake journey.
Digitalized, all-in-one medication labels combining data from different sources, and real-time label updates is another example of a smart solution that has been highly commended by patients.8 Real-time insight for the sites of patient’s understanding in label updates can also be highly beneficial in case of critical communications such as early study termination9 or medication recalls.
In addition, medication packages too can be of great support for patients to adhere to their dosing regimen. For example, smart packages—which are the traditional medication packages supplemented with electronic circuits, chips, and sensors—can track and verify medication intake till the individual pill or unit level and trigger alerts in case of inconsistencies to patients and sites.10,11,12 As an instance, in a Phase II Alzheimer study using smart blisters, a participant performed a wrong intake (he erroneously doubled his intake since he had forgotten his previous intake), that was immediately picked up and alerted by the system to site who could then connect and intervene directly with the patient.9
Such advanced medication tools can also be used to trigger motivational messages based on thresholds, or prompt specific questions in case of incorrect dosage or intake outside the allowed time window, or even identify behavioral changes and prevent potential cases of dropout.
Age and use of technology are often also raised as an area of concern. While younger people are believed to be more familiar with technology, studies have shown that elderly patients too are quite open and supportive of these technologies even if they have had limited to no prior experience with smartphone.8,9 Easy-to-use and simple features supported by clear and easy-to-understand training material is an important pre-requisite for elderly patients. In such population, medication compliance also remains very high (+90%) even after six months as exhibited in a recent study conducted for the elderly Asian population, by leveraging personalized patient notifications and support.10
And lastly, involving relatives or caregivers of a patient, and providing them with a read-only app or allowing them to perform certain activities on behalf of patient has also found to be very useful and highly recommended.
The erstwhile medication process is fractious involving several stakeholders, isolated systems and is often guided by a paper-based, manual approach involving hand-offs between multiple stakeholders. These include Contract Manufacturer Organizations (CMOs), depots, pharmacies, couriers, Interactive Response Technology (IRT) / Randomization & Trial Supply Management (RTSM) suppliers, medication destruction facilities in addition to clinical site personnel for dispensing and the patients—the most critical stakeholders—for intake.3
The process silos introduce a lot of inefficiencies and gaps in the process and are very labor-, time-and cost-intensive. What if there was a mechanism to integrate and interconnect all systems and stakeholders and ensure automated and seamless flow among diverse activities? What if all partners could have a real-time view of the medication process—where, what, and when? Or what if medication packages could automatically control parameters such as temperature, storage condition, etc. and alert sites and patients in case of concerns?
Recent advancements have shown that the above futuristic scenarios aren’t mere concepts anymore but are already becoming a reality. Collaboration between various technology, medication suppliers and pharma companies has enabled the creation of unified and integrated web portals and apps for patients and sites with real-time data flows, analysis, and insights.13,14,15
System integrations too can improve the data quality and integrity and pick up errors that might hitherto have gone undetected. For instance, in a recent study conducted for top-three pharma, a real-time RTSM integration with a barcode medication scanning tool resulted in an elimination of 10 kit assignment errors per month.13
Smart packages, that can measure temperature and storage conditions in real-time, or individual pill / unit removal as explained in previous section, can also have a significant impact with eliminating many of the manual, time, and cost-consuming activities. For example, the entire drug accountability overview or specific forms such as site medication destruction forms or prescription forms (a regular ask for direct to patient supplies) can be automatically generated from the system with one click. Reports have shown that ‘Temperature Out of Range’ error in shipments can count for 13 billion/year leading to a total loss of up to $35 billion/year considering the cost to replace and labor involved.16
While anytime, anyplace real-time insights on medication flows can bring significant value, having a secure stakeholder-based access management protocol in place is also an absolute necessity. For example, in direct-to-patient medication shipment scenarios, patient’s address and contact details can be securely stored in the system after participant’s consent is obtained but access must be strictly controlled. Only specific stakeholders such as courier services and home nurses can have access to these Personally Identifiable Information (PII), which at the end of the study should also be permanently deleted from the system.
Flexibility is a key word that we have learnt and put in practice at all levels and in a record time during the COVID-19 pandemic. Patients who were unable to travel owing to the social distancing norms, still needed to have access to life-saving drugs. As a result, alternative approaches combining technology and partnerships were put in place.
Tracking and verifying kit flows between different entities using simple technologies such as kit barcode or QR scanning have been implemented along the entire medication flow (e.g., Contract Manufacturing Organization, depot, sites, local pharmacy) even till the level of the patient confirming the right kit delivery by the courier using his/her own smartphone. Even implementing uber-like real-time notifications—providing insight into where the medication kit is—are items that are being considered.
Also offering sites the capability to define, even at an individual visit level whether the medication kit will be picked up or provided at the site, or shipped by courier to the patient’s home, or the local pharmacy, is another example of flexibility being introduced.
Flexibility to use alternative processes in case of issues is another example. For example, in case scanning technologies are not working, typing manual kit numbers should be available. Or in case the patient cannot confirm the receipt of courier delivery using his/her smartphone, the site can perform this activity remotely.
Lastly, introducing flexibility in the medication process was also a key ask even prior COVID. For example, providing sites with the ability to postpone treatments based on results (e.g., oncology treatments) and having digital engagements automatically updated to temporarily pause medication reminders and diary completion. Or even providing sites with the ability to combine medication handouts in line with patient’s holiday plans are just a few examples of flexible medication processes.
The possibilities of combining technology and partnership are endless but as with all novel processes, change management cannot be underestimated. Involving all stakeholders early and through the entire process i.e., from the design of the tool is highly recommended and proves extremely valuable in the long run.
Understandably, it won’t be a one size fits all approach and human interaction remains an important cog. Technology can never replace the site-patient interaction but can play a pioneering role in improving this relationship. Technology also doesn’t possess a magic wand to resolve all challenges, with medication regimen sometimes just not being realistic, requiring life science companies to go back to the drawing board and rethink.
In addition, to level up with the dynamic environment, new capabilities such as voice enabled packages, drones for drug delivery, personalized medicine, are being constantly explored and prototyped.
All of us understand that adoption of digital technologies in activities pertaining to medication in clinical trials has lagged for multitude of reasons including GMP ecosystem, lack in maturity of modern technologies, lack of guidelines etc. However, the COVID-19 pandemic situation has compelled us to break traditional silos and identify and implement novel approaches for carrying out medication management, placing patient at the center of care. Going back to the days of yore with manual approach governing limited patient and site support, fragmented ecosystems, non-integrated and rigid systems is a thing of past! As we enter the next generation of medication management fueled by innovative technologies and symbiotic partnerships, we can realize preventive, augmented, and embedded smart medication management. Let’s come together and go for it!
Dr. Hilde Vanaken is the Head Industry leader, Life Sciences and Healthcare, for TCS